Looking at the bubonic plague in colonial Senegal between 1914 and 1945, the author examines how colonizer and colonized changed their perceptions of the epidemic over time. Africans tenaciously resisted coercive and punitive plague control measures, and achieved a remarkable success in preventing the imposition of urban residential segregation. Whereas French bio-medical officials were initially convinced they would triumph over the plague pathogen, and contemptuously rejected the applied knowledge of African healers, many Africans regarded plague as biological warfare utilized by their conquerors. Attitudes changed as the plague became endemic from 1918 to 1945, imposing an especially severe burden on women. Coercive plague control measures such as compulsory vaccination, travel restrictions, and undignified burial, generated strong resistance, yet colonial officials gradually won the consent of a westernized minority of the African elite who came to equate Western bio-medicine with modernity. The call to segregate urban residents resonated throughout the plague years. The success of Africans in employing the law and, occasionally, the streets, to resist forced relocation and residential segregation was a remarkable achievement. Changing disease ecology played a complex role in the spread of bubonic plague, aided by such colonial capitalist initiatives as railways, ports, cash crop market farming, and labor migration. The powerful new pesticide DDT, administered by U.S. Army medics in 1944, probably ended the plague cycle, although in postcolonial Senegal, the structural issues lying behind the disease are not being addressed.